Indomethacin interferes with EGF-induced activation of ornithine decarboxylase in gastric cancer cells.
OBJECTIVE
Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation.


METHODS
The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells.


RESULTS
EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h.


CONCLUSIONS
Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.
Ishikawa
T
T
Yokohama City University, Yokohama, Japan.
Ichikawa
Y
Y
Tarnawski
A
A
Fujiwara
Y
Y
Fukuda
T
T
Arakawa
T
T
Mitsuhashi
M
M
Shimada
H
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000187:drug effects*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D009955:Ornithine Decarboxylase; D007213:Indomethacin